In a groundbreaking announcement, The Stanford University School of Medicine has said that its research team was able to sequence the genomes of an unborn baby, using only a blood sample from the mother. This of course makes the procedure much safer than trying to obtain a sample from the fetus while in the uterus.
Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics explained the approach:
“We’re interested in identifying conditions that can be treated before birth, or immediately after … Without such diagnoses, newborns with treatable metabolic or immune system disorders suffer until their symptoms become noticeable and the causes determined.”
The findings of his team are published in ‘Nature’ and are associated with another report from Washington University that achieved similar results using a technique developed at Stanford, which required an additional blood sample from the father. The advancement is much simpler, providing an easy procedure that needs only the mother present. One day, this kind of screening will likely be offered to most pregnant women as a routine.
Once the technique is further developed into a clinical process, the price of the test will obviously drop dramatically and doctors will be able to thoroughly screen for all known genetic problems well in advance of birth. Research has shown that sequencing just the exome can be enough to provide relevant information.
The new technique, however, enabled scientists to sequence the whole genome, and exome chains and they were able to find a feutus with DiGeorge syndrome, which is caused by a short deletion of chromosome 22. Symptoms of this particular problem can vary, but include cardiac and neuromuscular problems and cognitive impairment. Newborns with the condition often have feeding difficulties, heart defects and convulsions, due to excessively low levels of calcium.
Diana Bianchi, MD, executive director of the Mother Infant Research Institute at Tufts Medical Center, who was not involved in the Nature study said:
“The problem of distinguishing the mother’s DNA from the fetus’s DNA, especially in the setting where they share the same abnormality, has seriously challenged investigators working in prenatal diagnosis for many years … In this paper, Quake’s group elegantly shows how sequencing of the exome can show that a fetus has inherited DiGeorge syndrome from its mother.”
Bianchi is also chair of the clinical advisory board of Verinata Health Inc., a company that provides a fetal genetic test using earlier technology developed by Quake.
Parental diagnosis has been going on for decades, with tests for Spina Bifida, Down’s Syndrome and many others routinely given to expectant mothers. Other, more in depth testing, requires insertion of a needle into the amniotic sack. This procedure has a 0.5% chance of miscarriage, and is obviously undesirable, and this method is somewhat aggressive for the mother. The new test needs only a blood sample, and relies on the fact that freely floating cells from the fetus can be found in the mother’s bloodstream. By the third trimester, the quantity of fetal DNA can be as high as 30%.
Quake developed tests for Down’s Syndrome, using this technique as far back as 2008, but they were unable to provide a full DNA sequence. In the Stanford trials, two pregnant women were tested, one showed positive for DiGeorge syndrome the other was negative. The results of the trials were confirmed after the mothers gave birth. Although the tests were only retrospective, in a real situation, doctors would be better able to treat the baby immediately at birth, looking for heart issues and calcium levels from day one.
Study co-author Yair Blumenfeld, MD, a clinical assistant professor of obstetrics and gynecology at Stanford medical school said:
“Three years ago we were very excited about successfully validating non-invasive fetal aneuploidy detection … But we always knew that detecting fetal chromosomal abnormalities was just the tip of the iceberg, and that diagnosing individual gene defects was the future. This important study confirms our ability to detect individual fetal gene defects simply by testing mom’s blood.”
The team at Stanford is continuing the work and have filed a patent for a test that will eventually be used in maternity clinics around the world.
Written By Rupert Shepherd